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US 2022/0152168 A1Published application
Sequential heterologous boost oncolytic viral immunotherapy
AssigneesChildren's Hospital of Eastern Ontario Research Institute Inc., Turnstone Biologics Corp.
InventorsDavid Stojdl, Justyna KMIECIK, Michael F. BURGESS
Life of this patent
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Abstract
The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.
Claims94
A method of treating a tumor in a subject, wherein said tumor contains at least a first tumor-specific antigen, said method comprising the steps of:
- a) administering at least one dose of a prime, said prime being a composition capable of raising an immune response to at least the first tumor-specific antigen;
- b) administering at least one dose of a first boost said first boost comprising a first oncolytic virus, said first oncolytic virus comprising a nucleic acid capable of expressing at least a portion of said first tumor-specific antigen;
- c) administering at least one dose of a second boost, said second boost comprising a second oncolytic virus, said second oncolytic virus comprising a nucleic acid capable of expressing said at least a portion of said first tumor-specific antigen, and said second oncolytic virus being immunologically distinct from said first oncolytic virus;
- wherein the order of administration in the methods is step a), followed by step b), followed by step c).
1 more element
A sequential heterologous boost method of inducing an immune response to an antigen in a subject, comprising:
- a) administering to the subject a prime dose that comprises a composition that induces an immune response to the antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a first oncolytic virus that comprises a nucleic acid that expresses, in the subject, a protein that is capable of inducing an immune response to the antigen;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises a second oncolytic virus that comprises a nucleic acid that expresses, in the subject, a protein that is capable of inducing an immune response to the antigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus.
1 more element
A sequential heterologous boost method of inducing an immune response to an antigen in a subject, comprising:
- a) administering to the subject a prime dose that comprises a composition that induces an immune response to the antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a protein that is capable of inducing an immune response to the antigen, and a first oncolytic virus that does not comprise a nucleic acid that expresses the protein, in the subject, wherein the protein and the first oncolytic virus are administered to the subject together or separately;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises a protein that is capable of inducing an immune response to the antigen, and a second oncolytic virus that does not comprise a nucleic acid that expresses the protein, in the subject, wherein the protein and the second oncolytic virus are administered to the subject together or separately, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus.
1 more element
A sequential heterologous boost method of inducing an immune response to an antigen in a subject, comprising:
- a) administering to the subject a prime dose that comprises a composition that induces an immune response to the antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a protein that is capable of inducing an immune response to the antigen, and a first oncolytic virus that does not comprise a nucleic acid that expresses the protein, in the subject, wherein the protein and the first oncolytic virus are administered to the subject together or separately;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises a second oncolytic virus that comprises a nucleic acid that expresses, in the subject, a protein that is capable of inducing an immune response to the antigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus.
1 more element
A sequential heterologous boost method of inducing an immune response to an antigen in a subject, comprising:
- a) administering to the subject a prime dose that comprises a composition that induces an immune response to the antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a first oncolytic virus that comprises a nucleic acid that expresses, in the subject, a protein that is capable of inducing an immune response to the antigen;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises a protein that is capable of inducing an immune response to the antigen, and a second oncolytic virus that does not comprise a nucleic acid that expresses the protein, in the subject, wherein the protein and the second oncolytic virus are administered to the subject together or separately, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus.
1 more element
A sequential heterologous boost method of inducing an immune response to at least two antigens in a subject, comprising:
- a) administering to the subject a prime dose that comprises
- i. a composition that induces an immune response to at least a first and a second antigen;
- or
- ii. a first composition and a second composition, wherein the first composition induces an immune response to at least the first antigen, and the second composition induces an immune response to at least the second antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a first oncolytic virus that comprises:
- i. a first nucleic acid that expresses, in the subject, a first protein that is capable of inducing an immune response to at least the first antigen and
- ii. a second nucleic acid that expresses, in the subject, a second protein that is capable of inducing an immune response to at least the second antigen;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises a second oncolytic virus that comprises:
- i. a first nucleic acid that expresses, in the subject, a first protein that is capable of inducing an immune response to at least the first antigen and
- ii. a second nucleic acid that expresses, in the subject, a second protein that is capable of inducing an immune response to at least the second antigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus.
8 more elements
A sequential heterologous boost method of inducing an immune response to at least two antigens in a subject, comprising:
- a) administering to the subject a prime dose that comprises
- i. a composition that induces an immune response to at least a first and a second antigen;
- or
- ii. a first composition and a second composition, wherein the first composition induces an immune response to at least the first antigen, and the second composition induces an immune response to at least the second antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a first oncolytic virus that comprises a first nucleic acid that expresses, in the subject, a first protein that is capable of inducing an immune response to at least the first antigen and a second nucleic acid that expresses, in the subject, a second protein that is capable of inducing an immune response to at least the second antigen;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises:
- i. a first protein that is capable of inducing an immune response to at least the first antigen, and a second protein that is capable of inducing an immune response to at least the second antigen, wherein the first protein and the second protein are administered together or separately;
- and
- ii. a second oncolytic virus that does not comprise a nucleic acid that expresses, in the subject, the first protein, and does not comprise a nucleic acid that expresses, in the subject, the second protein, wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus;
- and wherein the second oncolytic virus is administered together or separately with the first protein, and wherein the second oncolytic virus is administered together or separately with the second protein.
8 more elements
A sequential heterologous boost method of inducing an immune response to at least two antigens in a subject, comprising:
- a) administering to the subject a prime dose that comprises
- i. a composition that induces an immune response to at least a first and a second antigen;
- or
- ii. a first composition and a second composition, wherein the first composition induces an immune response to at least the first antigen, and the second composition induces an immune response to at least the second antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises:
- i. a first protein that is capable of inducing an immune response to at least the first antigen, and a second protein that is capable of inducing an immune response to at least the second antigen, wherein the first protein is administered together or separately with the second protein;
- and
- ii. a first oncolytic virus that does not comprise a nucleic acid that expresses, in the subject, the first protein, and does not comprise a nucleic acid that expresses, in the subject, the second protein, and wherein the first oncolytic virus is administered together or separately with the first protein, and wherein the first oncolytic virus is administered together or separately with the second protein;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises a second oncolytic virus that comprises a first nucleic acid that expresses, in the subject, a first protein that is capable of inducing an immune response to at least the first antigen and a second nucleic acid that expresses, in the subject, a second protein that is capable of inducing an immune response to at least the second antigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus.
7 more elements
A sequential heterologous boost method of inducing an immune response to at least two antigens in a subject, comprising:
- a) administering to the subject a prime dose that comprises
- i. a composition that induces an immune response to at least a first and a second antigen;
- or
- ii. a first composition and a second composition, wherein the first composition induces an immune response to at least the first antigen, and the second composition induces an immune response to at least the second antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises:
- i. a first protein that is capable of inducing an immune response to at least the first antigen, and a second protein that is capable of inducing an immune response to at least the second antigen, wherein the first protein is administered together or separately with the second protein;
- and
- ii. a first oncolytic virus that does not comprise a nucleic acid that expresses, in the subject, the first protein, and does not comprise a nucleic acid that expresses, in the subject, the second protein, and wherein the first oncolytic virus is administered together or separately with the first protein, and wherein the first oncolytic virus is administered together or separately with the second protein;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises:
- i. a first protein that is capable of inducing an immune response to at least the first antigen, and a second protein that is capable of inducing an immune response to at least the second antigen, wherein the first protein and the second protein are administered together or separately;
- and
- ii. a second oncolytic virus that does not comprise a nucleic acid that expresses, in the subject, the first protein, and does not comprise a nucleic acid that expresses, in the subject, the second protein, wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus;
- and wherein the second oncolytic virus is administered together or separately with the first protein, and wherein the second oncolytic virus is administered together or separately with the second protein.
11 more elements
Dependencies are inferred from the claim text.